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Archive for the ‘Population Health Management, Genetics & Pharmaceutical’ Category


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Apr 22, 2020

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Dmitry Korkin is a professor of bioinformatics and computational biology at Worcester Polytechnic Institute, where he specializes in bioinformatics of complex disease, computational genomics, systems biology, and biomedical data analytics. I came across Dmitry’s work when in February his group used the viral genome of the COVID-19 to reconstruct the 3D structure of its major viral proteins and their interactions with human proteins, in effect creating a structural genomics map of the coronavirus and making this data open and available to researchers everywhere. We talked about the biology of COVID-19, SARS, and viruses in general, and how computational methods can help us understand their structure and function in order to develop antiviral drugs and vaccines.
This conversation is part of the Artificial Intelligence podcast.
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OUTLINE: 0:00 – Introduction 2:33 – Viruses are terrifying and fascinating 6:02 – How hard is it to engineer a virus? 10:48 – What makes a virus contagious? 29:52 – Figuring out the function of a protein 53:27 – Functional regions of viral proteins 1:19:09 – Biology of a coronavirus treatment 1:34:46 – Is a virus alive? 1:37:05 – Epidemiological modeling 1:55:27 – Russia 2:02:31 – Science bobbleheads 2:06:31 – Meaning of life
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Contagious

We are in the midst of a pandemic that is impacting people and society in ways that are hard to grasp. The most apparent impact is on physical health. It also effects our attitudes in society, our economy and our cultural life. Throughout history, humanity has had to face the challenge of understanding, managing and fighting viruses.

In the exhibition Contagious we are highlighting Nobel Prize-awarded researchers who have expanded our knowledge about viruses, mapped our immune system and developed vaccines. We also examine the perspectives from Literature and Economics Laureates about the impact of epidemics on life and society. Visit us at the museum or on these pages.

Museums have an important role to play in times of crisis, since they can help people tackle existential questions and provide a broader context. The Nobel Museum is about ideas that have changed the world. The Nobel Prize points to the ability of humans to find solutions to difficult challenges that we face time and time again. It is a source of hope, even in the midst of the crisis.

SOURCE

Nobel Prize Museum

https://nobelprizemuseum.se/en/whats-on/contagious/?utm_content=contagious_text

Coronavirus

On March 11 this year, the World Health Organization announced that the spread of the coronavirus should be classified as a pandemic, that is “an infectious disease that spreads to large parts of the world and affects a large proportion of the population of each country”. Today, nobody knows how many will die in this pandemic, or when, or if, we can have a vaccine against the disease.

SARS-CoV-2, or Severe acute respiratory syndrome coronavirus 2, is an RNA virus from the family coronavirus that causes the respiratory disease covid-19.

The virus was detected at the end of last year in the Wuhan sub-province of China, and in most cases causes milder disease symptoms that disappear within two weeks. But sometimes, especially in certain groups such as the elderly and people with certain other underlying illnesses, the infection becomes more severe and can in some cases lead to death.

The virus is believed to have zoonotic origin, that is, it has been transmitted to humans from another animal. Where the origin of the disease comes from, that is to say from which host animal the virus originates, is still unknown. However, the virus has close genetic similarity to a corona virus carried by some bats, which might indicate where the virus comes from.

This model shows the SARS-CoV-2 virus, which causes the illness covid-19. The globe-shaped envelope has a membrane of fat-like substances. Inside the envelope are proteins bound to RNA molecules, that contain the virus’s genes. Short spikes of proteins and longer spikes of glycoprotein stick out of the envelope and attach to receptors on the surface of attacked cells. The spikes, which are bigger at the top, give the virus its appearance reminiscent of the Sun’s corona. This where the coronavirus’s name comes from.

Testing is an important tool for tracking and preventing the spread of infection during an epidemic.

One type of test looks at if a person is infected by looking for traces of the virus’s RNA genetic material. The test is taken using a swab stick inserted into the throat. The small amounts of RNA or DNA that attach to the swab are analyzed using the PCR technique, which was invented by Kary Mullis in 1983. Ten years later he was awarded the Nobel Prize in Chemistry.

Another type of test looks for antibodies to the virus in the blood. This indicates that the person has had the disease.

https://nobelprizemuseum.se/en/coronavirus/

The first virus ever discovered

We have understood since the 19th century that many diseases are caused by microscopic bacteria that cannot be seen by the naked eye. It turned out that there were even smaller contagions: viruses. Research on viruses has been recognized with several Nobel Prizes.

https://nobelprizemuseum.se/en/the-first-virus-ever-discovered/

Spanish flu

The worst pandemic of the 20th century was the Spanish flu, which swept across the world 1918–1920.

The Spanish flu was caused by an influenza virus. American soldiers at military facilities at the end of World War I were likely an important source of its spread in Europe. The war had just ended, and the pandemic claimed even more lives than the war. Between 50 and 100 million people died in the pandemic.

The Red Cross, an international aid organization, which received the Nobel Peace Prize for its efforts during the war, also took part in fighting the Spanish flu. International Committee of the Red Cross received the prize in 1917, 1944 and 1963.

This photo shows personnel from the Red Cross providing transportation for people suffering from the Spanish flu in St. Louis, Missouri in the United States.

https://nobelprizemuseum.se/en/spanish-flu/

Polio

Polio is an illness that often affects children and young people and that can lead to permanent paralysis.

Polio is a highly infectious RNA virus belonging to the genus Enterovirus. The virus only infects humans and enters the body via droplets such as sneezing and coughing, or through contact with infected people’s feces. Usually, polio infects our respiratory and intestinal tract, but sometimes the virus spreads to the spinal cord and can then cause paralysis. The virus mainly affects children, but most of those infected show no or very mild symptoms.

Vaccines are a way to help our immune system fight viruses. The immune system is the body’s defence mechanism against attacks from viruses and bacteria. A number of Nobel Laureates have researched the immune system and contributed to the development of vaccines.

Hepatitis B

The virus can infect people without them becoming sick. Discoveries in the 1960s enabled both vaccines and tests to prevent the spread.

Hepatitis B can infect humans and apes, and is most common in West Africa and in sub-Saharan Africa. The disease also occurs in the rest of Africa, as well as in areas from the Caspian Sea through to China and Korea and further down to Southeast Asia.

Baruch Blumberg discovered the virus behind hepatitis B and developed a vaccine against the disease.

There are many varieties of hepatitis, or jaundice, that cause inflammation in the liver. When studying blood proteins from people from different parts of the world at the end of the 1960s, Baruch Blumberg unexpectedly discovered an infectious agent for hepatitis B. He showed that the infectious agent was linked to a virus of previously unknown type. The virus can infect people without them becoming sick. The discoveries enabled both vaccines and tests to prevent the spread through blood transfusions.

Baruch Blumberg was awarded the Nobel Prize in Physiology or Medicine 1976. He has summarized what the Nobel Prize meant to him.

https://nobelprizemuseum.se/en/hepatitis-b/

Yellow fever

Each year, Yellow fever causes about 30,000 deaths. The vaccine against yellow fever was produced in the 1930s. A work awarded the Nobel Prize.

Yellow fever is a serious disease caused by a virus that is spread by mosquitos in tropical areas of Africa and South America.

Each year, Yellow fever causes about 200,000 infections and 30,000 deaths. About 90% of the cases occur in Africa. The disease is common in warm, tropical climates such as South America and Africa, but it is not found in Asia.

You may think that the number of people infected would be decreasing, but since the 1980s the number of yellow fever cases has unfortunately increased. This is believed to be due to the fact that more and more people are living in cities, that we are traveling more than before, and an increased climate impact.

Since there is no cure for the disease, preventive vaccination is a very important measure. Max Theiler successfully infected mice with a virus in the 1930s, which opened the door to more in-depth studies. When the virus was transferred between mice, a weakened form of the virus was created that gave monkeys immunity. In 1937, Theiler was able to develop an even weaker version of the virus. This version could be used as a vaccine for people.

Max Theiler was awarded the Nobel Prize in Physiology or Medicine in 1951.

https://nobelprizemuseum.se/en/yellow-fever/

HIV/AIDS

In the early 1980s, reports began to emerge about young men that suffered from unusual infections and cancers that normally only affect patients with weakened immune systems. It turned out to be a previously unknown epidemic, HIV, which spread rapidly across the world.

HIV, which is an abbreviation of human immunodeficiency virus, is a sexually transmitted retrovirus that attacks our immune system. An untreated infection eventually leads to AIDS, or acquired immune deficiency syndrome. In 2008, French scientists Luc Montagnier and Françoise Barré-Sinoussi were awarded the Nobel Prize in Physiology or Medicine for the detection of human immunodeficiency virus.

Watch the interview where Françoise Barré-Sinoussi talks about what it is like to meet patients affected by the virus she discovered.

https://nobelprizemuseum.se/en/hiv-aids/

 

Viruses captured in photos

Viruses are incredibly small and cannot be seen in normal microscopes.

The electron microscope, which was invented by Ernst Ruska and Max Knoll in 1933, made it possible to take pictures of much smaller objects than was previously possible. Ernst Ruska’s brother, Helmut Ruska, was a doctor and biologist, and used early electron microscopes to make images of viruses and other small objects. The tobacco mosaic virus was the first virus captured on film. The development of the electron microscope has enabled increasingly better images to be taken.

Ernst Ruska was awarded the 1986 Nobel Prize in Physics together with Gerd Binnig and Heinrich Röhrer, who developed the scanning electron microscope.

Read more about Ernst Ruska – his life and research. https://www.nobelprize.org/prizes/physics/1986/ruska/facts/

https://nobelprizemuseum.se/en/viruses-captured-in-photos/

 

Epidemics and literature

When epidemics and pandemics strike the world, it isn’t just the physical health of people that are impacted but also ways of life, thoughts and feelings. Nobel Laureates in literature have been effected by epidemics and written about life under real and fictive epidemics.

The coronavirus crisis has had a dramatic impact on our lives and our view of our lives. Olga Tokarczuk is one of the authors who has reflected on this.

Tokarczuk argues that the coronavirus has swept away the illusion that we are the masters of creation and that we can do anything since the world belongs to us. She wonders if the pandemic has forced us into a slower, more natural rhythm in life, but also worries about how it may increase distrust of strangers and worsen inequality among people.

Orhan Pamuk has worked for many years on a novel about a bubonic plague epidemic that struck primarily Asia in 1901. The coronavirus crisis has caused him to consider the similarities between the ongoing pandemic and past epidemics throughout history.

He sees several recurring behaviors when epidemics strike: denial and false information, distrust of individuals belonging to other groups, and theories about a malicious intent behind the pandemic. But epidemics also remind us that we are not alone and allow us to rediscover a sense of solidarity. He writes in The New York Times.

https://nobelprizemuseum.se/en/epidemics-and-literature/

Economics Laureates on the current pandemic

Pandemics have wide-ranging impacts on the economy. Paul Romer and Paul Krugman are two economists who have been active in the public discourse during the coronavirus crisis.

Paul Romer has expressed concerns about the pandemic’s effects on the economy but is optimistic about the possibilities of technology. He supports widespread testing. Those who are infected have to stay home for two weeks while others can work and take part in other ways in society.

Paul Romer was awarded the prize “for integrating technological innovations into long-run macroeconomic analysis.” Paul Romer has demonstrated how knowledge can function as a driver of long-term economic growth. He showed how economic forces govern the willingness of firms to produce new ideas.

His thoughts are developed in his lecture during the Nobel Week 2018.

https://nobelprizemuseum.se/en/economics-laureates-on-the-current-pandemic/

 

Other SOURCE

https://www.nobelprize.org/

 

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Inflammation BioMarker C-Reactive Protein Guides Use of Systemic Glucocorticoids in Patients with COVID-19: The Effects on Mortality or Use of Mechanical Ventilation – (CRP) ≥20 mg/dL was associated with significantly reduced risk of Mortality or Mechanical Ventilation Efficacy

Reporter: Aviva Lev-Ari, PhD, RN

 

In patients with high levels of inflammation — at least 20 mg/dL — steroid treatment was associated with a 77% reduction in the risk of needing mechanical ventilation or dying (odds ratio [OR], 0.23).

Importantly, treating with steroids when CRP levels were less than 10 mg/dL was associated with an almost threefold increased risk of going on mechanical ventilation or dying (OR, 2.64).

“The laboratory test could potentially be very helpful,” Keller told Medscape Medical News.

https://www.medscape.com/viewarticle/934571

Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19

Article has an altmetric score of 299

Abstract

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Glucocorticoids are useful as adjunctive treatment for some infections with inflammatory responses, but their efficacy in COVID-19 is unclear. Prior experience with influenza and other coronaviruses may be relevant. A recent meta-analysis of influenza pneumonia showed increased mortality and a higher rate of secondary infections in patients who were administered glucocorticoids.3 For Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza, some studies have demonstrated an association between glucocorticoid use and delayed viral clearance.4-7 However, a recent retrospective series of patients with COVID-19 and ARDS demonstrated a decrease in mortality with glucocorticoid use.8 Glucocorticoids are easily obtained and familiar to providers caring for COVID-19 patients. Hence their empiric use is widespread.8,9

The primary goal of this study was to determine whether early glucocorticoid treatment is associated with reduced mortality or need for MV in COVID-19 patients.

DISCUSSION

The results of this study indicate that early treatment with glucocorticoids is not associated with mortality or need for MV in unselected patients with COVID-19. Subgroup analyses suggest that glucocorticoid-treated patients with markedly elevated CRP may benefit from glucocorticoid treatment, whereas those patients with lower CRP may be harmed. Our findings were consistent after adjustment for clinical characteristics. The public health implications of these findings are hard to overestimate. Given the global growth of the pandemic and that glucocorticoids are widely available and inexpensive, glucocorticoid therapy may save many thousands of lives. Equally important because we have been able to identify a group that may be harmed, some patients may be saved because glucocorticoids will not be given.

Our study reaffirms the finding of the as yet unpublished Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial that there is a subset of patients with COVID-19 who benefit from treatment with glucocorticoids.10 Our study extends the findings of the RECOVERY trial in two important ways. First, in addition to finding some patients who may benefit, we also have identified patient groups that may experience harm from treatment with glucocorticoids. This finding suggests choosing the right patients for glucocorticoid treatment is critical to maximize the likelihood of benefit and minimize the risk of harm. Second, we have identified patient groups who are likely to benefit (or be harmed) on the basis of a widely available lab test (CRP).

Our results are also consistent with previous studies of patients with SARS-CoV and MERS-CoV, in which no associations between glucocorticoid treatment and mortality were found.7 However, the results of studies examining the effect of glucocorticoids in patients with COVID-19 are less consistent.8,11,12

Few of the previous studies examined the effects of glucocorticoids in subgroups of patients. In our study, the improved outcomes associated with glucocorticoid use in patients with elevated CRPs is intriguing and may be clinically important. Proinflammatory cytokines, especially interleukin-6, acutely increase CRP levels. Cytokine storm syndrome (CSS) is a hyperinflammatory condition that occurs in a subset of COVID-19 patients, often resulting in multiorgan dysfunction.13 CRP is markedly elevated in CSS,14 and improved outcomes with glucocorticoid therapy in this subgroup may indicate benefit in this inflammatory phenotype. Patients with lower CRP are less likely to have CSS and may experience more harm than benefit associated with glucocorticoid treatment.

Several limitations are inherent to this study. Since it was done at a single center, the results may not be generalizable. As a retrospective analysis, it is subject to confounding and bias. In addition, because patients were included only if they had reached the outcome of death/MV or hospital discharge, the sample size was truncated. We believe glucocorticoid use in hospitalized patients excluded from the study reflects increased use with time because of a growing belief in their effectiveness.

Preliminary analysis from the RECOVERY study showed a reduced rate of mortality in patients randomized to dexamethasone, compared with those who received standard of care.10 These results led to the National Institutes for Health COVID-19 Treatment Guidelines Panel recommendation for dexamethasone treatment in patients with COVID-19 who require supplemental oxygen or MV.15 Our findings suggest a role for CRP to identify patients who may benefit from glucocorticoid therapy, as well as those in whom it may be harmful. Additional studies to further elucidate the role of CRP in guiding glucocorticoid therapy and to predict clinical response are needed.

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Severe COVID-19 in Patients experiencing Cytokine Storm: Positive Outcomes (faster respiratory recovery, a lower likelihood of mechanical ventilation, and fewer in-hospital deaths) of high dose methylprednisolone plus tocilizumab (Actemra, Genentech) vs Supportive Care Alone

Reporter: Aviva Lev-Ari, PhD, RN

 

“COVID-19-associated cytokine storm syndrome [CSS] is an important complication of severe acute respiratory syndrome coronavirus-2 infection in up to 25% of the patients,” lead author Sofia Ramiro, MD, PhD, told Medscape Medical News.

The researchers assessed outcomes of 86 individuals with COVID-19-associated CSS treated with high-dose methylprednisolone plus/minus tocilizumab, an anti-interleukin-6 receptor monoclonal antibody. They compared them with another 86 patients with COVID-19 treated with supportive care before initiation of the combination therapy protocol.

Participants with CSS had an oxygen saturation of 94% or lower at rest or tachypnea exceeding 30 breaths per minute.

They also had at least two of the following:

  • C-reactive protein > 100 mg/L;
  • serum ferritin > 900 μg/L at one occasion or
  • a twofold increase at admission within 48 hours; or
  • D-dimer levels > 1500 μg/L.

https://www.medscape.com/viewarticle/934567

Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study

  1. Sofia Ramiro1,2,
  2. Rémy L M Mostard3,
  3. César Magro-Checa1,
  4. Christel M P van Dongen1,
  5. Tom Dormans4,
  6. Jacqueline Buijs5,
  7. Michiel Gronenschild3,
  8. Martijn D de Kruif3,
  9. Eric H J van Haren3,
  10. Tom van Kraaij3,
  11. Mathie P G Leers6,
  12. Ralph Peeters1,
  13. Dennis R Wong7,
  14. Robert B M Landewé1,8

Author affiliations

 

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Novel SARS-CoV-2 sybodies

Reporter: Irina Robu, PhD

Absolute Antibody Ltd., a leader of the market in recombinant antibody products announced a partnership with University of Zurich to offer synthetic nanobodies against the receptor binding domain (RBD) of SARS-CoV-2. Under the partnership, the original nanobodies and recently engineered formats are now accessible to the global research community for use as serological controls and in COVID-19 therapeutic development. The synthetic nanobodies hold a particular potential for the development of inhalable drugs, which could suggest a convenient treatment option for the COVID-19 pandemic.

The laboratory of Markus Seeger at University of Zurich designs a rapid in vitro selection platform to generate synthetic nanobodies, sybodies, against the receptor binding domain (RBD) of SARS-CoV-2. Within a two-week timeframe, the lab had recognized more than 60 unique anti-RBD sybodies from combinatorial display libraries. The sybodies are “designed to mimic the natural shape diversity of camelid nanobodies, consequently allowing for an optimal surface complementarity to the limited hydrophilic epitopes on membrane proteins. Due to their high thermal stabilities and low production costs, sybodies demonstrate a promise for diagnostic and therapeutic applications.

Sybodies are perfectly suited to trap intrinsically flexible membrane proteins and thereby facilitate structure determination by X-ray crystallography and cryo-EM.
Additional research indicate that six of the sybodies bound SARS-CoV-2 spike protein with very high affinity, while five of those also inhibited ACE2, the host cell receptor to which SARS-CoV-2 binds to initiate the COVID-19 infection. Furthermore, two of the sybodies can at the same time bind the RBD, which could permit the construction of a polyvalent antiviral drug. The SARS-CoV-2 sybodies are therefore valuable tools for coronavirus research, diagnostics and therapeutic development.

Moreover, Absolute Antibody has used antibody engineering to fuse the nanobodies to Fc domains in different species, isotypes and subtypes. Absolute Antibody also offers supporting coronavirus research such as the production of gram quantities of human antibodies sequenced from recovering COVID-19 patients.

SOURCE

https://www.biocompare.com/Life-Science-News/562900-SARS-CoV-2-COVID-19-Research-News-Latest-Updates

 

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Three Stages to COVID-19 Brain Damage

Reporter: Irina Robu, PhD

According to a review published by Majid Fotuhi, PhD in the Journal of Alzheimer’s Disease, the impact of COVID-19 on the nervous system can be classified in three stages. In stage 1, viral damage is limited to the epithelial cells of the nose and mouth; stage 2, blood clots that form in the lungs can travel to the brain and in stage 3, the virus crosses the blood brain barrier and invades the brain.

Dr. Fotuhi recognized that patients with COVID-19 should have a neurological evaluation and an MRI before leaving the hospital, to distinguish if there are any anomalies. It has become increasingly obvious that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors write. As stated by authors of the review, the SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) that facilitates the conversion of angiotensin II to angiotensin. Subsequently ACE2 binds to respiratory epithelial cells, and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.” The cytokines, increase vascular permeability, edema and widespread inflammation which can cause small or large blood clots that affect multiple organs.

They concluded, that If SARS-CoV-2 crosses the blood–brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration. Scientists have limited information published about it, so doctors/scientists are uncertain why a virus this small can cause so many neurological things.

SOURCE

https://www.medscape.com/viewarticle/933131

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Does CSF Antibody Testing Confirm Coronavirus in the Brain?

Reporter: Irina Robu, PhD

It is still uncertain how COVID-19 invades the brain, but testing for antibodies in the cerebrospinal fluid may give some indication.  COVID-19 is typic Is characterized by respiratory illness and viral pneumonia with fever, cough, shortness of breath, and in severe cases, progression to acute respiratory distress syndrome. Recently, there have been a few investigations on what neurological complications can COVID-19 produce.

A case series of three patients attending an inner-city US hospital who had severe, laboratory-confirmed COVID-19 and encephalitis indicated that while only one had abnormal white blood cells or protein present in cerebral spinal fluid, all had evidence of immunoglobulin (IgM) antibodies. The cases include a 31-year-old woman with sickle cell disease who had a recent pulmonary embolus, a 34-year-old woman with sign of fever, shortness of breath and hypertension and a 64-year-old with hypertension. Dr. Benameur, from Emory University assessed cerebrospinal fluid inflammatory proteins and completed testing for SARS-CoV-2 using reverse transcription polymerase chain reaction (PCR).

The results show that two of the patients had normal white blood cell counts and protein levels. Yet, according to Dr. Benameur, even though the PCR in cerebral spinal fluid is negative, it doesn’t mean that the virus didn’t make it into the brain. The PCR test is good for some viruses, but it is not as reliable for this new coronavirus. Even though, all patients had encephalitis, the female patients also developed encephalomyelitis as indicated by inflammation in her brain and spinal cord.

Altogether, patients had symptoms affecting cortical and brainstem function at the peak of neurologic illness.

SOURCE

https://www.medscape.com/viewarticle/931964?src=mkm_covid_update_200608_mscpedit

 

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The race for a COVID-19 vaccine: What’s ahead ?

Reporter: Irina Robu, PhD

Researchers are conducting over 100 coronavirus vaccines studies, as they race to produce the first serum to protect people from COVID-19. Its uncertain which one would be successful, but what is certain is that without the vaccine, life would not return to normal anywhere on the world.

Usually, a vaccine takes 20 to 15 years to develop, but Moderna Therapeutics, a U.S. pharmaceutical company will test their vaccine on tens of thousands of people which are in critical phase 3. Even though many vaccines are tested now, only ten candidates are currently in clinical trials. The process to develop a vaccine is complicated and requires time and money.

However, in order to develop a vaccine, a pathogen has to be identified. After several in vitro trials, the vaccine is tested in mice, then in a non-human primate model. After these preclinical studies show  promising results, then the next step is to into clinical trials i.e. human testing. The human testing, occurs in various steps. The first step, phase 1 clinical trial is usually a small trial with 20 to 100 patients. The goal of this step is to asses the toxicity of the vaccine. Once, the first step clinical trials are completed and the results show positive result on toxicity and safety, progress to phase 2 trials can be started. Phase 2 clinical trials include 200 to 400 patients. In this phase, immunogenicity of the vaccine it is tested as well as how long it is effective.  Then, the last step is phase 3 clinical trial which can include as many as 30,000 people. The last phase it assesses whether the vaccine works on a broader scale.

Once the vaccine is effective, companies have to increase production to develop more than 7 billion doses. But due to the large number of people requiring this vaccine, scientists have to look at how to increase the manufacturing capability and distribution. In order to produce them effectively, a portfolio of vaccines have to be used.

 SOURCE

https://scopeblog.stanford.edu/2020/06/25/the-race-for-a-covid-19-vaccine-whats-ahead/

 

 

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 has been found. The placenta serves as the lungs, gut, kidneys, and liver of the fetus. This fetal organ also has major endocrine actions that modulate maternal physiology and, importantly, together with the extraplacental chorioamniotic membranes shield the fetus against microbes from hematogenous dissemination and from invading the amniotic cavity.

 

Most pathogens that cause hematogenous infections in the mother are not able to reach the fetus, which is largely due to the potent protective mechanisms provided by placental cells (i.e. trophoblast cells: syncytiotrophoblasts and cytotrophoblasts). Yet, some of these pathogens such as Toxoplasma gondii, Rubella virus, herpesvirus (HSV), cytomegalovirus (CMV), and Zika virus (ZIKV), among others, are capable of crossing the placenta and infecting the fetus, causing congenital disease.

 

The placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to manufacture the ACE2 receptor, the main cell surface receptor used by the SARS-CoV-2 virus to cause infection. These placental tissues also lack mRNA needed to make an enzyme, called TMPRSS2, that SARS-CoV-2 uses to enter a cell. Both the receptor and enzyme are present in only miniscule amounts in the placenta, suggesting a possible explanation for why SARS-CoV-2 has only rarely been found in fetuses or newborns of women infected with the virus, according to the study authors.

 

The single-cell transcriptomic analysis presented by the researchers provides evidence that SARS-CoV-2 is unlikely to infect the placenta and fetus since its canonical receptor and protease, ACE2 and TRMPSS2, are only minimally expressed by the human placenta throughout pregnancy. In addition, it was shown that the SARS-CoV-2 receptors are not expressed by the chorioamniotic membranes in the third trimester. However, viral receptors utilized by CMV, ZIKV, and others are highly expressed by the human placental tissues.

 

Transcript levels do not always correlate with protein expression, but the data of the present study indicates a low likelihood of placental infection and vertical transmission of SARS-CoV-2. However, it is still possible that the expression of these proteins is much higher in individuals with pregnancy complications related with the renin-angiotensin-aldosterone system, which can alter the expression of ACE2. The cellular receptors and mechanisms that could be exploited by SARS-CoV-2 are still under investigation.

 

References:

 

https://www.nih.gov/news-events/news-releases/placenta-lacks-major-molecules-used-sars-cov-2-virus-cause-infection

 

https://pubmed.ncbi.nlm.nih.gov/32662421/

 

https://pubmed.ncbi.nlm.nih.gov/32217113/

 

https://pubmed.ncbi.nlm.nih.gov/32161408/

 

https://pubmed.ncbi.nlm.nih.gov/32335053/

 

https://pubmed.ncbi.nlm.nih.gov/32298273/

 

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Study with important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection

Reporter: Aviva Lev-Ari, PhD, RN

Serological Testing WordCloud

Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection

Jeffrey SeowCarl GrahamBlair MerrickSam AcorsKathryn J.A. SteelOliver HemmingsAoife O’BryneNeophytos KouphouSuzanne PickeringRui GalaoGilberto BetancorHarry D WilsonAdrian W SignellHelena WinstoneClaire KerridgeNigel TempertonLuke SnellKaren BisnauthsingAmelia MooreAdrian GreenLauren MartinezBrielle StokesJohanna HoneyAlba Izquierdo-BarrasGill ArbaneAmita PatelLorcan OConnellGeraldine O HaraEithne MacMahonSam DouthwaiteGaia NebbiaRahul BatraRocio Martinez-NunezJonathan D. EdgeworthStuart J.D. NeilMichael H. MalimKatie Doores

Abstract

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy′s and St Thomas′ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.

SOURCE

https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1

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